RT Journal Article
T1 Influence of early identification and therapy on long-term outcomes in early-onset MTHFR deficiency.
A1 Yverneau, Mathilde
A1 Leroux, Stéphanie
A1 Imbard, Apolline
A1 Gleich, Florian
A1 Arion, Alina
A1 Moreau, Caroline
A1 Nassogne, Marie-Cécile
A1 Szymanowski, Marie
A1 Tardieu, Marine
A1 Touati, Guy
A1 Bueno, María
A1 Chapman, Kimberly A
A1 Chien, Yin-Hsiu
A1 Huemer, Martina
A1 Ješina, Pavel
A1 Janssen, Mirian C H
A1 Kölker, Stefan
A1 Kožich, Viktor
A1 Lavigne, Christian
A1 Lund, Allan Meldgaard
A1 Mochel, Fanny
A1 Morris, Andrew
A1 Pons, Mónica Ruiz
A1 Porras-Hurtado, Gloria Liliana
A1 Benoist, Jean-François
A1 Damaj, Léna
A1 Schiff, Manuel
A1 E-HOD Consortium, 
K1 EHOD
K1 MTHFR deficiency
K1 homocystinuria
K1 neurodevelopmental outcome
K1 newborn screening
K1 remethylation defects
AB MTHFR deficiency is a severe inborn error of metabolism leading to impairment of the remethylation of homocysteine to methionine. Neonatal and early-onset patients mostly exhibit a life-threatening acute neurologic deterioration. Furthermore, data on early-onset patients' long-term outcomes are scarce. The aims of this study were (1) to study and describe the clinical and laboratory parameters of early-onset MTHFR-deficient patients (i.e., ≤3 months of age) and (2) to identify predictive factors for severe neurodevelopmental outcomes in a cohort with early and late onset MTHFR-deficient patients. To this end, we conducted a retrospective, multicentric, international cohort study on 72 patients with MTHFR deficiency from 32 international metabolic centres. Characteristics of the 32 patients with early-onset MTHFR deficiency were described at time of diagnosis and at the last follow-up visit. Logistic regression analysis was used to identify predictive factors of severe neurodevelopmental outcome in a broader set of patients with early and non-early-onset MTHFR deficiency. The majority of early-onset MTHFR-deficient patients (n = 32) exhibited neurologic symptoms (76%) and feeding difficulties (70%) at time of diagnosis. At the last follow-up visit (median follow-up time of 8.1 years), 76% of treated early-onset patients (n = 29) exhibited a severe neurodevelopmental outcome. Among the whole study population of 64 patients, pre-symptomatic diagnosis was independently associated with a significantly better neurodevelopmental outcome (adjusted OR 0.004, [0.002-0.232]; p = 0.003). This study provides evidence for benefits of pre-symptomatic diagnosis and appropriate therapeutic management, highlighting the need for systematic newborn screening for MTHFR deficiency and pre-symptomatic treatment that may improve outcome.
YR 2022
FD 2022-05-09
LK http://hdl.handle.net/10668/22195
UL http://hdl.handle.net/10668/22195
LA en
DS RISalud
RD Apr 7, 2025